The purpose of this proposal is to analyze pancreatic secretions from patients with normal pancreas, pancreatitis and cancer of the pancreas for specific components or characteristic protein profiles which may assist in the early detection and diagnosis of pancreatic carcinoma. In view of the presumed role of free proteolytic enzymes in development of pancreatitis and possibly cancer of the pancreas and the finding of high concentrations of lysosomal hydrolases at the periphery of invading tumors, we propose to identify and determine some of these enzymes in pancreatic fluid. Their abnormal presence or quantity may indicate existing malignancy or premalignant changes and thus serve as a sensitive diagnostic marker. Clinical and experimental evidence suggests a correlation between diminished levels of pancreatic trypsin inhibitor and pancreatitis. We intend to explore the diagnostic significance of such an association by determining the concentration of trypsin inhibitor in pancreatic secretions of patients with suspected or existing pancreatitis or cancer of the pancreas. A recent study has indicated the existence of a genetically determined polymorphism of human trypsinogen. We shall examine the possibility that preponderance or high levels of one of the two trypsinogen variants may be correlated with a predisposition of a segment of the population to pancreatitis and (or) cancer of the pancreas. We have developed exceedingly sensitive methods capable of detecting pancreatic proteases, trypsin inhibitor and lysosomal hydrolases in the picomole range as well as rapid procedures for the separation of trypsinogen variants and their quantitation which we intend to adapt to the work proposed. Pancreatic fluid will be collected by pancreatic ductal cannulation of patients with suspected pancreatic disease and scheduled for endoscopic retrograde cholangiopancreatography.